POS1550 IMPACT OF ORAL, SELECTIVE, ALLOSTERIC TYROSINE KINASE 2 (TYK2) INHIBITOR, DEUCRAVACITINIB, ON PSORIASIS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM A PHASE 2 TRIAL
Authors: A. B. Gottlieb, A. Armstrong, J. F. Merola, A. Napoli, M. Nowak, S. Banerjee, T. Lehman, P. J. Mease
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> TYK2 mediates signaling of key cytokines (eg, IL-23) involved in plaque psoriasis (PsO) and psoriatic arthritis (PsA) pathogenesis. Deucravacitinib (DEUC) is a first-in-class, oral, selective, allosteric TYK2 inhibitor approved in multiple countries for the treatment of adults with PsO. This was based on superiority of DEUC to apremilast and placebo (PBO) in a variety of PsO disease activity measures in 2 phase 3 trials in patients with moderate to severe PsO <sup>[1,2]</sup>. In addition, DEUC was efficacious on multiple measures of arthritis severity compared with PBO in a phase 2 trial in patients with active PsA who had ≥1 PsO lesion (≥2 cm) <sup>[3]</sup>. In patients with body surface area (BSA) ≥3% at baseline (mild to severe; 80% of patients in this trial), a greater proportion of patients achieved a ≥75% reduction in Psoriasis Area and Severity Index (PASI 75) with DEUC treatment (6 mg QD: 42.4%, <i>P</i>=0.01; 12 mg QD: 59.6%, <i>P</i>&lt;0.0001) vs PBO (20.4%) at week (wk) 16. <h3>Objectives</h3> This analysis further evaluated the impact of DEUC on PsO in patients with PsA in the phase 2 trial. <h3>Methods</h3> The phase 2 double-blind PsA trial randomized patients (N=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. After wk 16 (Part A), patients could enroll in an optional, double-blind period until wk 52 (Part B). In Part B, patients receiving DEUC who achieved minimal disease activity (MDA) at wk 16 continued DEUC treatment to wk 52. Measurements of PsO disease activity, including mean BSA, mean PASI score, and achievement of PASI and BSA thresholds, were assessed. <h3>Results</h3> At baseline (BL), PsO characteristics were generally comparable across treatment groups, with most patients (≥74%) having mild to moderate PsO (BSA &lt;10% and PASI ≤12; <b>Table 1</b>). At wk 16, significant decreases from BL in mean PASI score were observed with DEUC treatment vs PBO both in patients with mild to moderate PsO as well as in those with moderate to severe PsO (BSA ≥10%; PASI &gt;12) (<b>Figure 1</b>). These significant changes in PASI were observed in the mild to moderate PsO population even with very low BL PASI scores. Significant decreases in PASI from BL were observed with DEUC treatment vs PBO in both patients with background csDMARD use (DEUC 6 mg, -4.0 and 12 mg, -4.9 vs PBO, -2.3; <i>P</i>&lt;0.05 for both) and those without csDMARD use (-3.7 and -4.0 vs -2.5, respectively; <i>P</i>&lt;0.001, for both). At wk 16, a greater proportion of patients treated with DEUC vs PBO achieved PASI ≤1 in patients with mild to severe PsO (DEUC 6 mg, 32.2% and 12 mg, 44.2% vs PBO, 18.5%) and in patients with moderate to severe PsO (23.1% and 28.6% vs 0.0%, respectively). In mild to severe PsO, decreases in mean PASI score at wk 16 were maintained through wk 52 in patients who continued treatment with DEUC 6 mg (absolute PASI score, wk 16: 2.39, wk 52: 1.22) and 12 mg (wk 16: 0.64, wk 52: 0.24). <h3>Conclusion</h3> Treatment with DEUC significantly improved PsO in patients with PsA, regardless of BL PsO severity and background csDMARD use. Of note, improvement in the subgroup of patients with moderate to severe PsO in this trial was comparable to that observed in the phase 3 POETYK PSO-1 trial in patients with moderate to severe PsO <sup>[1]</sup>. <h3>References</h3> [1]Armstrong A, et al. <i>J Am Acad Dermatol</i>. 2023;88(1):29-39. [2]Strober B, et al. <i>J Am Acad Dermatol</i>. 2023;88(1):40-51. [3]Mease PJ, et al. <i>Ann Rheum Dis.</i> 2022;81:815-822. <h3>Acknowledgements</h3> This study was sponsored by Bristol Myers Squibb. <h3>Disclosure of Interests</h3> Alice B Gottlieb Consultant of: AnaptysBio, Amgen, Avotres, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, and Xbiotech (stock options for an RA project), Grant/research support from: AnaptysBio, Janssen, Novartis, Ortho, Sun Pharma, and UCB, April Armstrong Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis, Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant, Grant/research support from: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Dermira, Kyowa Hakko Kirin, and UCB, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB, Andrew Napoli Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Lehman Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sun Pharma, and UCB.